PROJECT SUMMARY/ABSTRACT The overall goal of this multi-disciplinary proposal is to create a novel, high-throughput, autologous, ex vivo model system that recapitulates cancer biology, immuno-biology, vasculature formation, and multiple aspects of the tumor microenvironment (TME). Such a system would create a heretofore unprecedented platform for scientists to study human tumors in a controlled setting to evaluate fundamental cancer properties (e.g. angiogenesis, cell migration, metastases) with the ultimate goal of novel diagnostic and therapeutic development. Specifically, this project seeks to determine the feasibility of our ex vivo ?tumor on a chip? device platform to serve as both: (1) a high throughput system to evaluate multiple cancer cell types and non-tumor cell components of the TME using ?off the shelf? reagents to address hypothesis-driven research and (2) precisely study human tumors and autologous non-tumor cell types in a personalized fashion. When successful, this system will address multiple pressing needs in cancer biology; chiefly, the ability to model the complex TME in vitro in a precise and autologous fashion. This research proposal addresses all stated goals of the IMAT program: innovation, cancer-relevance, substantial improvement over current technologies, and transformative potential. This device platform would provide cancer biologists with a powerful, precise, and novel technique to model human cancers in the laboratory.